The overall objective of this proposal is the application of physico-chemical rationale and techniques to the study of physiological and pathological processes. Certain biological fluids (bile, intestinal content, plasma and lymph) contain lipids solubilized in aqueous systems. Other lipids, particularly those of the membranes of cells and the membranes of intracellular organelles contain lipids which are not soluble but are structured in such a way as to combine fluidity with stability. Further, inherited deficiencies of enzymes involved in the catabolism of complex sphingolipids result in the accumulation of structured lipid accumulations found in brains and other tissues of patients with various forms of the familial lipidoses. Finally, certain lipids, occurring for instance in adipose tissue, adrenal glands, gonads, liver and atherosclerotic lesions, contain lipids in phases separated from the aqueous system. These phases are liquids or more structured liquid-crystalline or crystalline phases. Since it is important to know the physical state of lipid molecules in aqueous systems - biologic systems being aqueous systems - the long term objectives are: a) to continue the study of phase equilibria and physical state of model systems of lipids in the dry state, in bulk aqueous systems and at the air-water interface, b) to examine the structure and physical characteristics of the phases found (solids, liquid crystals, liquids), c) to correlate these model systems with actual physiological and pathological phenomena, especially: 1) The nature of the lipid lesions of human atherosclerosis. 2) The structure and physicochemical characteristics of biological membranes, serum lipoproteins, and abnormal lipid deposits in the various lipidoses. 3) The role of bile in the absorption of lipids and in cholesterol gallstone formation. BIBLIOGRAPHIC REFERENCES: The thermal transitions and structural properties of 5 -cholestan-3 -yl esters of aliphatic acids. B.E. North, G.G. Shipley, and D.M. Small. Biochimica et Biophysica Acta (1976) 424: 376-385. Conformational and thermodynamic properties of apo A-I from human plasma high density lipoproteins. A.R. Tall, G.G. Shipley, and D.M. Small. Journal of Biological Chemistry (1976) 251: 3749-3755.